The objective of these studies has been to demonstrate that nephrogenous cAMP provides a sensitive and specific in vivo bioassay of parathyroid function. In a group of 58 patients with primary hyperparathyroidism, iPTH was elevated in 42 (71%) and nephrogenous cAMP in 52 (90%) of patients. Based on the physiology of cAMP clearance and the findings of this study, a parametric expression for urinary cAMP (nmol/min/100 ml GFR) was developed. This simple analysis and expression revealed abnormal values in 90% of hyperparathyroid patients. Patients with primary hyperparathyroidism and episodic hypercalcemia constitute a common and difficult diagnostic problem; the abnormal parathyroid function in these patients may be easily defined by lack of normal suppression of nephrogenous cAMP in response to calcium infusion. Nephrogenous cAMP has also been used to help develop diagnostic criteria in the ill-defined subtypes of idiopathic hypercalciuria. Patients with "renal leak" hypercalciuria display high fasting calcium excretion, secondary hyperparathyroidism and normal parathyroid suppressibility. Patients with "absorptive" hypercalciuria display normal fasting calcium excretion and suppression of nephrogenous cyclic AMP in response to oral calcium.